Testicular germ cell tumors in adolescents - results of the protocol MAHO 98 and the identification of good risk patients.

BACKGROUND: In adolescents aged 10-15 years germ cell tumors of the testis (TGCT) are rare and information for a risk adapted therapy limited. AIMS OF THE STUDY: The protocol MAHO 98 for patients (pts) with TGCTs is stratified according to age, stage and histology. Pts ≥ 10 years received after tumororchiectomy 2 courses (crs) PVB and restaging. Residual tumor was resected and therapy continued in regard to inital stage and response. Chemotherapy: PVB: cisplatin (20 mg/m²/day 1-5), vinblastine (3 mg/m²/day 1+2), and bleomycin (15 U/m²/day 1-3). For consolidation 1 crs PVB has been given to stage II patients with CR. In case of PR, 2 crs PEB (vinblastine substituted by etoposide 100 mg/m²/day 1-3) or relapse 3 crs PEI (bleomycin substituted by ifosfamide 1 500 mg/m²/day 1-5) were given. RESULTS: Between Jan 1998 and Dec 2005, 34 pts (≥ 10 year) were registered, 31 fulfilled the inclusion criteria. Median age: 15;6 years; months (range 13;5-20;2 ). Lugano staging: IA n=14, IB n=2, IC n=3, IIA n=4, IIB n=6, IIC n=1, IIIC n=1. The stage IIIC pt received preoperative chemotherapy, all other pts had tumororchiectomy first. Residual tumor after 2 crs PVB was detected in 4 pts and was resected. Late relapses occurred in 2 pts and were cured by additional therapy. All patients are surviving. CONCLUSION: Young patients with TGCT stage I and II have an excellent prognosis and further reduction of therapy has to be considered.

Testicular germ cell tumors in boys <10 years: results of the protocol MAHO 98 in respect to surgery and watch & wait strategy.

UNLABELLED: In 1982 the GPOH opened the 1st protocol for germ cell tumors (GCTs) of the testis (MAHO 82). Here the results of the 5th version (MAHO 98) will be offered for boys <10 year of age.In MAHO 98 watch and wait (w&w) strategy after inguinal tumororchiectomy was widened from 2 to 10-year-old boys with YST stage IA (group I); other invasive measures were omitted. Thus the prognostic impact of a non-recommended surgery like transscrotal operation +/- conventional biopsy (group II) can be evaluated.Clinical diagnosis and staging by ultrasound and tumor marker. In blurry cases, a frozen section was recommended to confirm the diagnosis by histology intraoperatively. Indications for adjuvant chemotherapy were: YST stage IA without elevated AFP, YST stage>IA and all mixed malignant GCTs.From 1998 till 2005 128 boys <10 years with a testicular GCT were registered. HISTOLOGY: YST n=76, teratoma n=46, mixed malignant GCT n=6. Tumor stage IA: n=101. All teratoma patients survive event-free. At all, only 19/82 patients with a malignant GCT received chemotherapy including 5 patients with a tumor progress after w&w (2/49 group I and 3/15 group II patients, respectively) and 1 patient (YST IIIA) with relapse after adjuvant chemotherapy. Transscrotal surgery (n=18) or tumorenucleation (n=6) remained without event. Indeed all patients survived.Prognosis of boys <10 year with a testicular GCT is excellent as ~80% will be cured by high inguinal tumororchiectomy alone. w&w is feasible and safe even after not recommended surgery if suitable follow-up is assured at least in stage IA cases.

Telemicroscopic conferences for children of the Perm territory with suspected or proven malignant solid tumors.

BACKGROUND: Malignant solid tumors are rare events in childhood and adolescence. Therefore central review of the histology and standardized grading are requested for accurate risk estimation and facilitate a tumor risk adapted treatment. AIMS OF THE STUDY: To abandon the time consuming transportation of tumor material over long distances to the specialized institution by implementation of an internet based consultation system. METHODS: A microscope combined with a videocamera (situated in Perm) and the personal computers of each of 4 cooperating institutions (in Perm, Kiel, Koeln, Duesseldorf) has been equipped with the special software Mikroskopkonferenz. Additional videocameras allow the transmission of the cooperators to each other. Headsets are used to avoid reecho. As a prerequisite an internet connection with a 54 KBits capacity has to be provided. RESULTS: Between January and December 2009, 26 children (median age 2; 5 years, 12 females and 14 males) with suspected or proven malignant solid tumors have been discussed in 11 telemicroscopic conferences by international cooperators. CONCLUSION: This cooperation demonstrates the proof of principle to obtain second opinions in short time over far distances for seldom diseases on a scientific level.

[Quality improvement of multiple choice examinations: in psychiatry, psychosomatic medicine, psychotherapy, and neurology]. / Qualitätsverbesserung von Multiple-Choice-Prüfungen: In Psychiatrie, Psychosomatik, Psychotherapie und Neurologie.

We describe a continuous improvement process in planning, performance, and evaluation of multiple choice examination questions in psychiatry, neurology, psychosomatic medicine, and psychotherapy. We analyzed 640 multiple choice questions of 1,419 students during a period of 4 years. Crucial changes concerned the abolishment of problematic question types, implementation of validated new question formats, extension of case-based questions, elongation of question stems, quantitative evaluation of item difficulty, discriminatory value, and the introduction of a peer review system. Consequences of these improvements were greater item difficulty (average 18%) and discriminatory value (average 67%) and reduced post hoc analysis times. Introduction of peer reviews resulted in longer preparation time, which was however appreciated by the peers due to a clear improvement in item quality.

Pathology and molecular biology of teratomas in childhood and adolescence.

The biologic behaviour of teratomas depends on various interdependent clinical and epidemiologic variables such as the age at diagnosis, sex, tumor site, histology which all correlate to different cytogenetic and molecular biologic aberrations. Thus, testicular teratomas of infancy are generally benign. Accordingly, prepubertal teratomas show no cytogenetic or molecular genetic aberrations. In contrast, postpubertal testicular teratomas can present as clinically malignant tumors and may show complex cytogenetic aberrations such as the isochromosome 12p, which is pathognomonic of malignant germ cell tumors. Notably, teratomas of both age groups show an at least partial erasure of the genomic imprinting, correlating with their origin from primordial germ cells. The Kiel Pediatric Tumor Registry includes 541 teratoma specimens, and among these, the most frequent tumor sites (in descending order) are: the sacrococcygeal region (33.8 %), the ovaries (31.2 %) and the testes (10.5 %). Rare localizations include the mediastinum, the retroperitoneum, the head and neck region as well as the central nervous system. The WHO classification of germ cell tumors distinguishes mature and immature teratomas as well as teratomas with malignant transformation. In immature teratomas, primitive neuroectodermal structures predominate. According to the grading system (Gonzalez-Crussi, 1982), mature teratomas (G0) are more frequent (54.5 %) than immature teratomas (G1-G3, 45.5 %). Only 7.8 % of all teratomas show the highest grade of immaturity (G3). The frequency of additional microscopic foci of malignant yolk sac tumor correlates with the grade of immaturity. In sacrococcygeal teratomas, the yolk sac tumor microfoci may give rise to a malignant relapse after incomplete resection. The rare teratomas with malignant transformation contain components with "conventional" somatic type malignancy such as leukaemia, carcinoma or sarcoma. Here, molecular genetic analysis has demonstrated the origin of the somatic malignancy from a malignant transformation within the germ cell tumor with retention of the cytogenetic changes characteristic of malignant germ cell tumors.

The malignant potential of teratomas in infancy and childhood: the MAKEI experiences in non-testicular teratoma and implications for a new protocol.

UNLABELLED: Since 1982, mature and immature teratomas have been recruited into the MAHO and MAKEI protocols of the German Society for Pediatric Oncology and Hematology (GPOH) for testicular and non-testicular germ cell tumors in order to study the epidemiology and clinical behaviour of teratomas. Patients were registered in the epidemiologic German Childrens Cancer Registry and the GPOH Childrens Tumor Registry for pathological review. Patients with immaturity grade 2 and 3 according to Gonzales-Crussi were eligible for adjuvant chemotherapy. The consecutive protocols MAKEI 83/86/89 have been published previously in detail (Klin Paediatr 1997; 209: 228-234, Med Pediat Oncol 1998; 31: 8-15) and will be compared to the data of MAKEI 96. For this comparison, 274 patients from MAKEI 83/86/89 and 261 patients from MAKEI 96 are evaluable. RESULTS: 1) EFS after complete tumor resection has been estimated to 0.96 +/- 0.01 in both observation periods. 2) Incomplete tumor resection remains the main risk factor for relapse (EFS 0.55 +/- 0.09). 3) The relapse rate declined from 13.9 % in MAKEI 83/86/89 to 9.5 % in MAKEI 96. 4) In MAKEI 83/86/89 four newborns with teratoma died due to perioperative complications and nine children as a result of tumor progression, whereas in MAKEI 96 no newborn died, only one child died from tumor progression, and another child died during long time observation for another reason (meningitis). 5) In accordance to the experience of the MAKEI 83/86/89 studies, no child of the MAKEI 96 study presented with yolk sac tumor at recurrence if adjuvant chemotherapy was administered during first-line treatment because of immaturity. In contrast, more than half of the children with tumor recurrence after watch and wait strategy had yolk sac tumor in addition to teratoma.

Patients with extreme obesity: change in mental symptoms three years after gastric banding.

OBJECTIVE: Extreme obesity causes grave psychosocial and psychopathological problems in addition to somatic morbidity. One possible treatment is gastric banding, a surgical reduction of stomach volume. The aim of this study was to investigate whether gastric banding leads to lasting change in: 1) the Body Mass Index (BMI); 2) social factors such as work and partnerships, eating behavior, anxiety and depression symptoms; and 3) health related quality of life. METHOD: We surveyed a sample of 50 adipose women (BMI > 40 kg/m2). Primary outcome measures were self-reported changes on the scales of the Three-Factor Eating Questionnaire (TFEQ), the Hospital Anxiety and Depression Scale (HADS-D), and the Health Survey (SF-36). RESULTS: In comparison with the control group, we observed significant changes in BMI (p < 0.01) and the existence of a partnership (p < 0.01), on all three scales of the TFEQ (p < 0.01), on both scales of the HADS-D (anxiety: p < 0.05; depression:p < 0.01), and on all scales of the SF-36 Health Survey (p between < 0.05 and < 0.01 in every case). The most marked changes in all the qualities investigated occurred within the first 12 months of surgery. CONCLUSIONS: Three years after gastric banding, positive changes in BMI reduction, partnership, eating behavior, anxiety, depressive symptomatology, and health related quality of life could be observed. There was also a significant correlation between BMI reduction and reduction firstly on the depression scale (HADS-D) and secondly on the SF-36 scales for physical functioning (PHFU), role physical (ROPH), mental health (PSYC), and vitality (VITA).

AFP/beta-HCG secreting CNS germ cell tumors: long-term outcome with respect to initial symptoms and primary tumor resection. Results of the cooperative trial MAKEI 89.

PURPOSE: The aim of the present study was to evaluate survival and factors influencing long-term outcome of patients with AFP/beta-HCG secreting (non-seminomatous) central nervous system germ cell tumors (secCNSGCT), who were prospectively collected in the cooperative MAKEI (German: maligne Keimzelltumoren) 89 protocol. PATIENTS AND METHODS: Between January 1989 and January 1994, 28 patients with secCNS GCT were registered and treated according to the MAKEI 89 protocol. The protocol recommended, after a clinically or histologically proven diagnosis and cisplatin-based chemotherapy, a resection of residual tumor and craniospinal irradiation (30 Gy) with a tumor boost (20 Gy). RESULTS: The estimated (Kaplan-Meier) event-free survival (EFS) of protocol patients is 0.57 +/- 0.09 (n = 28) and the relapse-free survival (RFS) is 0.67 +/- 0.10 (at five and ten years). With respect to long-term survival, the combination of marked neurological symptoms at diagnosis along with primary tumor resection seem to be the main negative prognostic risk factors (Fisher exact test p < 0.05). CNS dissemination at diagnosis can also be considered as a negative risk factor as 3 of 5 patients with primary dissemination died of the disease. CONCLUSION: Cisplatin-based three agent chemotherapy followed by resection of the residual tumor and craniospinal irradiation (CSI) with tumor boost is a successful and well-tolerated treatment for secCNSGCTs. The possibility of a clinical diagnosis based on MRI and tumor markers together with the use of modern neurosurgical techniques gives us the chance to postpone or even avoid major surgery. This gives an additional chance to reduce acute morbidity and further decrease late effects.

No prognostic effect of additional chromosomal abnormalities in children with acute lymphoblastic leukemia and 11q23 abnormalities.

This study characterized the additional chromosomal abnormalities (ACA) associated with 11q23 rearrangements in 450 infants and children with acute lymphoblastic leukemia (ALL) and examined the impact of these ACA on survival. Overall, 213 (47%) cases had ACA but the incidence varied according to patient age and 11q23 subgroup. Infants and patients with t(4;11)(q21;q23) had the lowest incidence of ACA (50/182 (27%) and 57/216 (26%) respectively), whereas patients with del(11)(q23) had the highest incidence (66/93 (71%)). Del(11)(q23) abnormalities were heterogeneous and occasionally secondary to t(9;22)(q34;q11.2). Thus, patients with del(11)(q23) comprised a separate biological entity, which was clearly distinct from those with an 11q23 translocation. The most frequent specific ACA were trisomy X (n = 38), abnormal 12p (n = 32), abnormal 9p (n = 28) and del(6q) (n = 19). The presence of ACA did not change the 5 year event-free survival estimates among children (56% (95% Cl 46-65%) vs 62% (54-69%)) or infants (22% (15-29%) vs 18% (9-29%)), nor when the different 11q23 subgroups were analyzed separately. This study has conclusively demonstrated that there is no prognostic effect of secondary chromosomal changes in association with 11q23 abnormalities in childhood ALL. However, characterization of these ACA is important to determine their potential role in initiation of MLL driven leukemogenesis.

[Morphological variability of synovial sarcoma in childhood]. / Morphologische Variabilität des synovialen Sarkoms im Kindesalter.

We report on an unusual locally recurrent plantar soft tissue sarcoma in a 7-years-old boy. Due to an unusual morphology a clear diagnosis was initially not possible. The histologically different recurrent tumor was classified as synovial sarcoma by means of immunohistochemistry, ultrastructural and molecular analysis. This case demonstrates the variable morphological appearance of synovial sarcoma and the value of modern diagnostic procedures in such circumstances.

[Soft tissue malignancies in childhood and adolescence. Pathology and clinical relevance based on data from the kiel pediatric tumor registry]. / Weichteilmalignome bei Kindern und Jugendlichen -- Pathologische Anatomie und ihre klinische Relevanz. Mit Daten aus dem Kieler Kindertumorregister.

Soft tissue malignancies in childhood and adolescence encompass a wide variety of histologically and genetically different tumor entities. In the files of the Kiel Pediatric Tumor Registry, 4,272 soft tissue malignancies were collected since 1977. Rhabdomyosarcomas are by far the most frequent sarcomas (44.6 % of the cases), followed in decreasing order of frequency by the family of Ewing tumors (peripheral primitive neuroectodermal tumors and extraosseous Ewing's sarcomas; altogether 22.3 %), malignant peripheral nerve sheath tumors (8.1 %), synovial sarcomas (5.0 %), leiomyosarcomas (3.2 %), fibrosarcomas (2.4 %), extrarenal malignant rhabdoid tumors (2.0 %), and alveolar soft tissue sarcomas (1.1 %). A further group (11.3 %) includes rare tumors, intermediate fibrohistiocytic tumors, and unclassified sarcomas. Embryonal rhabdomyosarcomas are 2.5 times more frequent than the alveolar rhabdomyosarcomas, which are prognostically unfavorable and located predominantly in the extremities and the trunk. With regard to clinical findings, histology, molecular biology and prognosis, embryonal and alveolar rhabdomyosarcomas have to be considered as two different tumor types. The family of Ewing tumors includes extraosseous Ewing's sarcoma and peripheral primitive neuroectodermal tumors (synonym: malignant peripheral neuroectodermal tumors), the former tumors without and the latter with neural differentiation. Many cases of infantile malignant peripheral nerve sheath tumors and infantile fibrosarcomas are low-grade malignancies and prognostically more favorable than their "adult" counterparts.

[Proliferation and hTERT expression in neuroblastoma]. / Proliferationskinetik und hTERT-Expression beim NeuroblastomUntersuchungen zum Zusammenhang.

BACKGROUND: Transcription of the catalytic subunit of telomerase, human Telomerase Reverse Transcriptase (hTERT), and increased tumor cell proliferation are powerful prognostic factors in neuroblastoma. We therefore investigated their relationship in a large group of neuroblastomas. METHODS: RT-PCR analysis was used to discriminate between the various hTERT transcripts. Tumor cell proliferation was assessed immunohistochemically using two different cell-cycle specific antibodies and the results were compared by statistical analysis. RESULTS AND CONCLUSIONS: 54 out of 115 neuroblastomas showed hTERT transcripts, 25 of which also possessed full-length transcripts. Full-length hTERT transcripts were correlated with MYCN-amplification, with a Ki67-proliferation index > or = 25% and a repp86-proliferation index > or = 10% (p<0,0001), but only a Ki67-proliferation index > or = 25% was associated with general hTERT transcription (p=0,001). Our data confirm the close relationship between hTERT transcription and tumor cell proliferation and further strengthen the exceptional prognostic power of the repp86-proliferation index.

An approach for cure: PEI-chemotherapy and regional deep hyperthermia in children and adolescents with unresectable malignant tumors.

BACKGROUND: Elevated temperatures of 40 - 44 degrees C increase the actions of various anticancer drugs including N-lost derivatives, cytotoxic antibiotics and platinum analoga. In clinical usage thermochemotherapy (TCH) should facilitate surgical resection and ameliorate local tumor control. PATIENTS AND METHODS: From 07/1993 to 12/2002 a total of 39 patients have been enrolled onto a phase-II study (female = 24, male = 15, age 1 - 37.5 years, median 5.2). Among these, 24 patients had extracranial non-testicular germ cell tumors and 15 patients soft tissue or chondrosarcomas. INDICATION: locoregional relapse (n = 29) or unresectable tumor after neoadjuvant chemotherapy (n = 10). Among these two groups, there were ten patients with poor response or progressive disease under primary or relapse chemotherapy. Ten out of the 29 relapse patients had more than one relapse. Tumor site: pelvis (30), abdomen (4), head and neck (2), proximal leg (2) and lumbar spine (1). Thermochemotherapy (TCH): 1800 - 2000 mg ifosfamide/m (2) and 100 mg etoposide/m (2) on days 1 - 4 and 40 mg cisplatin/m (2) on days 1 + 4 combined with regional deep hyperthermia (42 - 44 degrees C, 1 h) on days 1 + 4. RESULTS: In 39 protocol patients a total of 166 TCH courses (332 heat sessions) were applied. 20 patients achieved complete response, and 10 patients achieved partial response. TCH was followed by surgical tumor resection in 28/39 patients and/or radiotherapy in 13/39 patients. At a median follow-up of 27 months, outcome in this high-risk patient population was 22 NED, 3 AWD, 12 DOD, 2 DOC. Five year event free (EFS) and overall survival (OS) for the whole study cohort was 0.39 +/- 0.11 (20/39 patients) and 0.52 +/- 0.11 (25/39 patients), respectively. CONCLUSION: TCH shows substantial therapeutic efficacy and facilitates complete tumor resection in 14 out of 28 operated patients. Multimodal treatment including TCH, surgical resection and/or radiotherapy leads to sustained remission in the majority of patients with locoregional tumor recurrence. The therapeutic effect is most pronounced, if TCH is administered at first relapse. Due to the clinical and histologic heterogeneity the number of patients eligible for TCH is limited. Therefore, a more valid assessment of treatment efficacy can only be made by a matched-pair comparison in cooperation with the clinical registers.

Patient stratification based on prednisolone-vincristine-asparaginase resistance profiles in children with acute lymphoblastic leukemia.

PURPOSE: To confirm the prognostic value of a drug resistance profile combining prednisolone, vincristine, and l-asparaginase (PVA) cytotoxicity in an independent group of children with acute lymphoblastic leukemia (ALL) treated with a different protocol and analyzed at longer follow-up compared with our previous study of patients treated according to the Dutch Childhood Leukemia Study Group (DCLSG) ALL VII/VIII protocol. PATIENTS AND METHODS: Drug resistance profiles were determined in 202 children (aged 1 to 18 years) with newly diagnosed ALL who were treated according to the German Cooperative Study Group for Childhood Acute Lymphoblastic Leukemia (COALL)-92 protocol. RESULTS: At a median follow-up of 6.2 years (range, 4.1 to 9.3 years), the 5-year disease-free survival probability (pDFS) rate +/- SE was 69% +/- 7.0%, 83% +/- 4.4%, and 84% +/- 6.8% for patients with resistant (PVA score 7 to 9), intermediate-sensitive (PVA score 5 to 6), and sensitive (SPVA score 3 to 4) profiles, respectively (sensitive and intermediate-sensitive v resistant, P

Ovarian sex cord-stromal tumors in children and adolescents.

PURPOSE: To develop diagnostic standards and a risk-adapted therapeutic strategy for ovarian sex cord-stromal tumors (OSCST). PATIENTS AND METHODS: Fifty-four patients were prospectively enrolled as follow-up patients onto the German Maligne Keimzelltumoren protocols. Surgical protocols and histopathology were reviewed centrally (53 patients with complete data). Surgery included ovariectomy in 18 patients, salpingo-ovariectomy in 34 patients, and hysterectomy in one patient. Patients with stage IA tumors were followed-up at regular intervals, whereas nine patients with stage IC and six patients with stage II to III tumors were treated with cisplatin-based chemotherapy. RESULTS: International Federation of Gynecology and Obstetrics stage was IA in 27 patients, IC in 21 patients, II in three patients, and III in three patients. After a median follow-up of 59 months (range, 6 to 193 months), event-free survival +/- SD was 0.86 +/- 0.05 (47 of 54 patients) and overall survival was 0.89 +/- 0.05 (49 of 54 patients). Prognosis correlated with stage (event-free survival +/- SD: IA, 1.0 [27 of 27 patients]; IC, 0.76 +/- 0.09 [16 of 21 patients]; and II/III, 0.67 +/- 0.19 [four of six patients]; P =.02). Ten of 15 patients treated with chemotherapy, including four of six stage II to III patients, are alive after a median follow-up of 33 months. CONCLUSION: On the basis of a standardized clinical and histopathologic assessment, risk-adapted therapeutic strategies for OSCST can be evaluated. Considering our experience, we would recommend that stage IA tumors be followed up at regular intervals, whereas we would recommend cisplatin-based chemotherapy in stage IC tumors with preoperative rupture or malignant ascites, especially those with high mitotic activity. Finally, cisplatin-based chemotherapy also seems to be effective in advanced-stage tumors.

Clinical heterogeneity in childhood acute lymphoblastic leukemia with 11q23 rearrangements.

To assess the clinical heterogeneity among patients with acute lymphoblastic leukemia (ALL) and various 11q23 abnormalities, we analyzed data on 497 infants, children and young adults treated between 1983 and 1995 by 11 cooperative groups and single institutions. The substantial sample size allowed separate analyses according to age younger or older than 12 months for the various cytogenetic subsets. Infants with t(4;11) ALL had an especially dismal prognosis when their disease was characterized by a poor early response to prednisone (P=0.0005 for overall comparison; 5-year event-free survival (EFS), 0 vs 23+/-+/-12% s.e. for those with good response), or age less than 3 months (P=0.0003, 5-year EFS, 5+/-+/-5% vs 23.4+/-+/-4% for those over 3 months). A poor prednisone response also appeared to confer a worse outcome for older children with t(4;11) ALL. Hematopoietic stem cell transplantation failed to improve outcome in either age group. Among patients with t(11;19) ALL, those with a T-lineage immunophenotype, who were all over 1 year of age, had a better outcome than patients over 1 year of age with B-lineage ALL (overall comparison, P=0.065; 5-year EFS, 88+/-+/-13 vs 46+/-14%). In the heterogeneous subgroup with del(11)(q23), National Cancer Institute-Rome risk criteria based on age and leukocyte count had prognostic significance (P=0.04 for overall comparison; 5-year EFS, 64+/-+/-8% (high risk) vs 83+/-+/-6% (standard risk)). This study illustrates the marked clinical heterogeneity among and within subgroups of infants or older children with ALL and specific 11q23 abnormalities, and identifies patients at particularly high risk of failure who may benefit from innovative therapy.

Prognostic value of tumor size, metastases, extension into bone, and increased tumor marker in children with malignant sacrococcygeal germ cell tumors: a prospective evaluation of 71 patients treated in the German cooperative protocols Maligne Keimzelltumoren (MAKEI) 83/86 and MAKEI 89.

PURPOSE: To evaluate the prognostic value of metastases, extension into bone, and alpha-fetoprotein (AFP) elevation in children with malignant sacrococcygeal germ cell tumors (GCTs) prospectively collected in two cooperative Maligne Keimzelltumoren (MAKEI) protocols (83/86 and 89). PATIENTS AND METHODS: Between October 1983 and October 1995, 76 of 210 registered patients with sacrococcygeal primaries presented either with pure yolk sac tumor, embryonal carcinoma (EC), or yolk sac tumor and EC mixed with immature and mature teratoma elements. Stages T1 and T2 disease were diagnosed in 15 and 61 children, respectively, 41 patients had metastases, and 35 children presented with extension into bone. At diagnosis, 22 children had an AFP elevation of less than 10,000 ng/mL. Thirty-six children showed an AFP level between 10,000 and 100,000 ng/mL, and 12 patients had values of greater than 100,000 ng/mL. Five patients died of complication during treatment and were excluded from further evaluation. Seventy-one patients could be analyzed. RESULTS: The 5-year relapse-free survival rate (RFS, Kaplan-Meier) was 0.76 +/- 0.03 (54 of 71 patients; median observation time, 54 months after diagnosis). The RFS of patients with and without metastases was different, but not significantly so (0.71 v 0.82). The outcome of patients with extension into bone (n = 31) and without this extension (n = 40) was 0.71 versus 0.80 (RFS, 5 years). Above-normal AFP level had no prognostic significance (P =.52). CONCLUSION: In children with malignant sacrococcygeal GCTs treated with an intensive, short-interval, platinum-based regimen, the stage, extent of metastases, extension into bone, and AFP level had no prognostic significance.

The influence of preoperative chemotherapy and surgical technique in the treatment of hepatoblastoma--a report from the German Cooperative Liver Tumour Studies HB 89 and HB 94.

UNLABELLED: Despite the success of chemotherapy in the treatment of hepatoblastoma (HB), the complete surgical resection of the primary liver tumour and metastases is the most important factor for survival. METHODS: From 1989 to 1998, 141 children with HB were treated in the German Cooperative Paediatric Liver Tumour Study HB 89 and HB 94. The study determines the results of surgical strategy, which adapts the procedure at the initial operation to the tumour extension in the liver and the occurrence of metastases. RESULTS: The median follow-up of the survivors was 72 months (range 24 - 132 months). 98/141 (78 %) patients were alive and 31/141 (22 %) died. 12/141 (8.5 %) children had no surgical treatment. A complete resection of the primary tumour was achieved in 107/129 (83 %) cases. Forty-eight children were primary resected and eighty-one children were operated on after initial chemotherapy. In 36 cases, an atypical tumour resection, in 90 cases an anatomical liver resection, was performed. Three children were transplanted. There was no perioperative death. 14/48 (30 %) children with primary tumour resection had microscopical or macroscopical residual tumour in the liver. Despite the larger number of advanced HB in the primary chemotherapy group, an incomplete tumour resection was performed in only 15/78 (19 %) cases after liver resection (p < 0.044). 14/36 (38 %) cases with atypical tumour resection and only 16/90 (18 %) cases with anatomical liver resection had residual tumours in the liver (p < 0.019). These results underline the necessity for preoperative chemotherapy in all HB, which was accepted in the following study HB 99. Atypical tumour resection should be avoided because of the higher rate of incomplete tumour resections and local relapse compared to the group with anatomical tumour resection.